Pharmaceutical manufacturers have the responsibility to offer the market safe and reliable drug products. Compendial testing makes it possible for healthcare professionals, pharma businesses, and regulatory entities to ensure that only the best medicines reach the hands of patients.
What is compendial testing?
Compendial testing refers to a series of principles and procedures devised to guarantee the identity, efficacy, and safety of pharmaceutical products. Also known as pharmacopeial standards, compendial requirements are put in place to attain the best quality control and manufacturing practices.
The quality of essential medicines is specified in The International Pharmacopoeia. Drug products are considered to be essential medicines when they satisfy the needs of the majority of the population in countries that are WHO Member States (source).
Other examples of pharmacopeias include:
- The European Pharmacopeia
- The British Pharmacopeia
- The United States Pharmacopeia
- The Japanese Pharmacopeia
- The Indian Pharmacopeia
- The Chinese Pharmacopeia
Compendial testing for formulated products and active ingredients
New drug applications (NDAs) are not always approved after their initial submission. It is possible for regulatory agencies to require additional product testing before a pharmaceutical product’s drug compatibility is proven.
Analytical testing procedures to guarantee a universal standard of good drug product quality include:
- Description of active ingredients and solid oral dosage forms
- Identification of active pharmaceutical ingredients (APIs)
- Impurity testing
- Sterility testing
- Dissolution studies
- Tablet disintegration testing
- Tablet friability testing
- Tablet hardness testing
Descriptions of active ingredients and solid oral dosage forms
Description tests offer qualitative physical analysis of drug products. These include ideal visual characteristics such as the product’s size, shape, color, and identifying markings. In case a particular batch of product doesn’t match the information provided by a description test, then it is immediately considered to be defective.
Pharmacopeias can’t include description testing, as the physical description of a pharmaceutical product is to be provided by the manufacturer. Branded products containing the same substances as generic products can be identified by using specific markings.
Identification of active pharmaceutical ingredients (APIs)
The identity or presence of active ingredients must be determined via identification tests. A large variety of analytical techniques and methods are used for this purpose. When studying drug formulations, it may be necessary to extract the drug substance from the dosage form.
Techniques such as near-IR spectroscopy may be used to study APIs without having to isolate them. The best spectroscopy technique to analyze API content depends on the characteristics of the compound being studied. Identification testing must have enough specificity to distinguish between similarly structured compounds. This includes starting materials and degradation products.
An assay is used to determine the purity of substances as well as the amount of API available in finished products. Normally, an assay procedure analyzes the difference between the sample and an external standard solution of known concentration. Commonly used assay methods include high-performance liquid chromatography, UV spectroscopy, and titration.
Impurity testing procedures are required to determine the quality of drug products. There are three main categories of impurities to consider:
- Organic impurities: The synthesis or degradation of biological products can result in the creation of organic impurities. In case the structure and toxicology of the impurities in contaminated products are not recognized, then they are classified as unidentified impurities. Examples of organic impurities include raw materials, by-products, reagents, ligands, catalysts, intermediates, and degradation products.
- Inorganic impurities: These environmental contaminants are commonly a by-product of the manufacturing process. This makes them relatively easy to identify. Inorganic impurities tend to be determined during the testing of a drug substance, rather than in the final dosage form. Inorganic salts, heavy metals, reagents, and ligands are examples of inorganic impurities.
- Residual solvents: Common solvents like benzene and chloroform may end up contaminating a drug product due to their use during the manufacturing process. Chromatographic procedures can be used to determine the existence of residual solvents.
Chemical testing for microbiological contamination is a regulatory requirement. Compendial methods for product sterility testing must not allow for any chance of accidental microbial contamination or false positive results. Usually, 14-day incubation times are required for successful compendial sterility testing, but some methods allow for the procedure to be completed in less than a week.
Two separate media must be used as compendial microbiological methods for sterility testing. To analyze aerobic bacteria and mold contamination, a culture of soybean casein digest medium is used. In turn, a fluid thioglycollate medium is implemented for the study of both aerobic and anaerobic bacteria. Turbidity in the culture can be used for fungal detection and similar activities.
Dissolution testing methods are routinely used for quality control in the pharmaceutical industry. Dissolution outcomes are commonly integral to release testing decisions. During the development of pharmaceutical products, dissolution method development helps optimize the product formulation and manufacturing processes.
The same set of techniques are implemented during the approval and post-approval stages, and must periodically be performed during routine manufacturing. Different types of equipment for dissolution test development exist.
For instance, the United States Pharmacopoeia (USP) specifies five distinct standardized dissolution apparatuses:
- Reciprocating cylinder
- Flow-through cell
- Reciprocating disk
Tablet disintegration testing
This product stability testing procedure measures the ability of a tablet product to break down and allow the API to be absorbed by the body. This testing procedure is performed by simulating the conditions of the stomach in a lab setting.
Tablets are lowered into a beaker of degassed or sonicated deionized water in a special contraption and kept at 37°C. Recovered samples can be analyzed using high-performance liquid chromatographic procedures or ultraviolet-visible spectroscopy. Disintegration testing is also useful during the early stages of drug formulation.
Tablet friability testing
Friability testing of drug products allows one to certify they will be able to go through the packing and transportation processes without being compromised. Tablets are subjected to a certain amount of physical stress to then be inspected for any damage or lost mass. Mechanisms for standardized friability testing have been approved by various pharmacopeias.
Tablet hardness testing
In a similar way to friability testing, tablet hardness testing applies physical force to drug products. The difference lies in that hardness testing is meant to determine the breaking point and structural integrity of tablets.
Which compendium to use and when to use it?
All drug products must be approved by the regulatory bodies of each region where they are to be distributed. The required compendial testing procedures are those that can be used to create pharmacopeial monographs that satisfy regulatory requirements:
- For drug products containing new substances, the development phase of the drug discovery process will determine the testing methods.
- Testing methods may become compendial methods when they are submitted to the pharmacopeia.
- Pharmacopoeias typically request testing methods from drug manufacturers. The purpose of this is to include the information in the pharmacopeia.
- Provided testing methods become the official compendial methods. If no testing methods are provided, then the pharmacopeia may develop its own methods.
Compendial testing services
Valentia Analytical is your ideal partner when it comes to analytical method validation and analytical method development services. Our expert team has extensive knowledge and experience with all facets of analytical method development, including the provision of solutions that respect the requirements set by the ICH or any other pharmacopoeial method.
From raw material testing using the most advanced chromatography techniques to preparing finalized products for manufacturing, Valentia Analytical can enhance your R&D efforts and certify you deliver the best pharmaceutical products to the market.